Posts Tagged ‘smallpox’

The Center for Disease Control and Prevention, AKA the CDC, America's central medical laboratory has recently had multiple problematic episodes. I was trying to follow up on the vials of smallpox virus that were found in an old refrigerator that the FDA apparently had forgotten, The question, of course, was whether the virus samples were long dead or still viable. They had been sent to the CDC to have that highly significant issue resolved.

Since then there has been a followup announcement, but also several articles on significant issues with procedures and safety at the CDC itself. The first was published in The New York Times, AKA NYT, (as well as in other papers, but I get the NYT daily on my iPad , so saw it there first). The startling title was "C.D.C. Closes Anthrax and Flu Labs after Accidents." The current director of the CDC, Dr. Thomas Frieden, called the lab/agency "the reference laboratory to the world," but admitted there had been a series of accidents (actually lapses in set safety procedures), in the recent past, that were quite frightening.

A month ago potentially infectious samples of anthrax, a bacteria found naturally in soil and commonly affecting wild and domesticated animals worldwide, causing an extremely serious, but rare illness in people, were sent to labs that were not equipped to deal with them (anthrax would normally be handled only with the highest level of protective biosafety gear and procedures (BSL-4). The CDC also has a rather simplistic YouTube video discussing anthrax's use as a potential bioterrorism weapon, but in this case 62 or more CDC employees were potentially exposed to the bacteria in the course of their work.

The good news is it appeared nobody was in danger; all those employees were given the anthrax vaccine and also begun on antibiotics. The background information available online says there has never been person to person spread of the disease.

It appears that it's exceedingly tough to get rid of anthrax in the environment; I'll go over the classic historical example of how careful government researchers have been with its spores..

In the 1940s, British scientists used a small Scottish island (Gruinard) for germ warfare research. That island, thoroughly contaminated with anthrax spores, remained off-limits for forty+ years before extraordinary efforts, begun in 1986, rendered it safe for ordinary use. The surface of the island was only 484 acres; it was sprayed with a herbicide, then all dead vegetation was burned off. Next 200 tons of formaldehyde solution was diluted in 2,000 tons of seawater and sprayed over the entire island. Perforated tubing was used to ensure that 50 liters of solution were applied to every square meter being treated.

Later the effectiveness of the decontamination process was assessed by taking two duplicate sets of soil samples. Each was tested at two major government labs. Anthrax spores were detected only in "small quantities in a few places." These specific areas were treated in July 1987, followed by further soil sampling in October 1987. No further traces of anthrax spores were found.

Blood samples from local rabbits were also tested for anthrax antibodies. No such antibodies were found.

Following these measures, a farmer grazed part of his flock of sheep on the island for six months. The sheep were inspected monthly by the District Veterinary Officer, and returned to the mainland in October 1987 in excellent condition.

On April 24, 1990, 4 years after the decontamination works had been completed, a Defense Minister visited the island and removed the safety signs, indicating that the island had finally been rendered safe. Then, per agreement the island was sold back to the heirs of the original owner for the WWII sale price of £500.

But a senior British archeologist said he still wouldn't set foot on the island; he was concerned because of potentially infectious particles found in some of his digs.

Yet another NYT piece, "Ticking Viral Bombs, Left in Boxes," this one written by a distinguished physician, Lawrence K. Altman, M.D. recalls the irony of the outcry for mass smallpox vaccination of our entire U.S. population after 9-11 (when no Iraqi supply of the deadly bacterium was ever located), contrasted with the recent finding of six vials, two with live smallpox bugs, being found in in Bethesda, almost within "spitting distance" of our center of government.

In 2011 the Birmingham Mail reviewed a tragic lab accident which led to the last known smallpox death . The city, now England's second largest, was a site of a medical research laboratory associated with the local medical school. Viral particles got into an air duct and a photographer whose studio was one story up from the lab became the last known case of active smallpox and died from the disease in spite of having been vaccinated twelve years before

Dr. Altman discusses the pros and cons of eradicating the last two known stocks of the virus, one at the CDC, the other in a Russian lab in Siberia. Even if the natural virus is finally and totally eliminated , a rogue group may well be able to re-establish their own supply from the known genetic sequence of smallpox.

Lastly I saw a NYT article with an even more disturbing title, "After Lapses, C.D.C. Admits a Lax Culture at Labs." CDC workers had somehow shipped a dangerous strain of avian influenza to a poultry research lab run by the Department of Agriculture. Known as H5N1, the virus had killed more than half of the 650 people who had been infected with it since 2003. Again there were no deaths from this mistake.

After all of this recent furor plus the historical examples, I'm heartily in favor of the idea that's been broached saying such dangerous organisms should be confined to a minimal number of labs and even those clearly need to tighten up their standards.

I was glancing through The Wall Street Journal. this morning (that period is intentional as I found out recently in their 150th anniversary issue) and saw an article about smallpox, that old enemy of mankind. The CDC issued a media statement saying six vials labeled with the technical name of the disease, variola, had been found in an old storage room belonging to an FDA lab that is on the NIH Bethesda, Maryland facility. Forty-two years ago the FDA took over that lab, among others, and only now were those labs being moved to the main FDA location in the DC area. The vials themselves date back ~60 years and now will be tested to see if the material in them is viable (i.e., live smallpox viruses).

I reviewed the CDC's Bio-hazard Safety Levels; they range from 1 to 4 with more serious infectious agents occupying the higher levels. A BSL-3 agent can cause serious or deadly disease, but either doesn't spread from person to person (at least not easily) and/or has a preventive or treatment known. Plague, rabies virus and West Nile fit into this category. Smallpox is obviously a BSL-4 bug, the most dangerous kind and in the company of Ebola virus. A February 15, 2012 Reuters article, "How secure are labs handling the world's deadliest pathogens?" talked about the precautions used in such a lab in Galveston, Texas. The boss there got entry by swiping a key card, was scanned by 100+ closed-circuit cameras as he opened seven additional locked doors before he reached the lab where another card swipe and a fingerprint scan were necessary for entry. The Washington Post article on the recently found vials has a six-minute video on BSL-4 procedures with a comment that there are three over-lapping types of safety precautions: those for containment of the hazardous material; those for personal protection and overall administrative factors.

And this may get you into BSL-3

The air flow and exhaust systems used in Galveston, the full-body suits with their own air supply and the intruder drills that are conducted all made me somewhat more comfortable. But that's in a government-funded laboratory. Even in the United States, a private-funded lab may not be subject to the same rules and regulations, Elsewhere the procedures that must be followed vary. In 2011 there were 24 known BSL-4 labs in the world with six in the U.S. (The GAO said we had considerably more.) In 2013 there was considerable protest in Boston over the proposed BSL-3 and BSL-4 lab there.

We don't see these anymore.

I've written about smallpox before, but a brief history, available online on a dermatology website was worth reviewing. The disease likely originated in Africa about 12,000 years ago. caused a major epidemic during an Egyptian-Hittite war in 1,350 B.C.E and left typical scars on the mummy of Pharaoh Ramses V who died in 1157 B.C.E. It got to Europe somewhere between the 5th and 7th centuries C.E.; millions died in Europe and the Western Hemisphere before Edward Jenner developed vaccination in 1796. The term came from the Latin word for cow (vaca), as Jenner used fluid from a cowpox-infected dairymaid's hand to inoculate an eight-year-old boy. In 1967 WHO estimated there were 15 million cases of smallpox and 2 million deaths from the disease. Total smallpox deaths over the past 12,000 years have been estimated at 300-500 million, more than all the world wars combined.

By 1980 the World Health Organization declared the globe smallpox-free. In this country, we quit vaccinating the general population in 1972 and stopped giving the inoculation to new military personnel in 1990.

My wife's old shot record shows she got her first vaccination against small pox in 1956 and the last booster in 1980. We were both assigned to bases in the Far East in the early and mid 80s. I can't find my military vaccination record from that time frame, but logically wouldn't have had a booster after 1986 when I got back to a base in Texas. Since immunity is unlikely to last more than ten years, at this stage we'd both be vulnerable to smallpox, like most everyone else.

The only known supplies of the virus remained in government laboratories in the United States and Russia. There has been considerable international protest against keeping those specimens alive starting in the early 1990s, but thus far neither country wants to give in to that pressure. One rationale was the genetic structure of the virus was known, so it could conceivably be recreated by terrorists.

In 2004 the CDC said they had stockpiled enough smallpox vaccine on hand to vaccinate everyone in the United States. I haven't found any updates on that statement. But the U.S. military was still giving those shots to personnel going to USCENTCOM areas (the Middle East and the "stans") until the middle of May, 2014, to Korea for another two weeks and to some special mission troops after that with an end date unspecified.

So now it's the middle of 2014 and, in one manner or another, smallpox is still lingering, fortunately not as an active disease. The CDC is testing those re-found vials of the virus and we'll hear in a couple of weeks is they were still viable.

Vaccines have a humble beginning. Smallpox was the first infection that people tried to prevent using a method called variolation, developed in China and India, in which dried material from a smallpox scab was ground up and then administered to a well individual, blowing the powder into their nose and hopefully giving them a mild case of smallpox and long-term immunity to the disease.

It originated from the observation that people who survived a previous smallpox infection somehow become resistant to getting the infection again. It was thought that by artificially infecting an unaffected person, the process could protect the individual from the dire malady.

Smallpox is an ancient disease; a great online article by Stefan Riedel, an MD, PhD from the Baylor University Medical Center, traces its history over an estimated 12,000 years, with Egyptian mummies from 3,000 to 3,500 years ago showing typical facial scars.

The Antonine Plague, which lasted from CE 165 to 180, most likely was smallpox (though possibly measles). It killed 2,000 per day in the Roman Empire with total deaths estimated at nearly seven million. Many scholars feel it significantly contributed to the downfall of the empire.

Ancient Chinese documents show that variolation was practiced in the Song dynasty in China (CE 960 to 1279). Legend has it that the Song emperor had lost his eldest son to smallpox, so he traveled deep into the forest of a high mountain and sought help from a reclusive nun. The woman was known as a holy healer, and she passed on the technique of variolation to save the ancient Chinese royal family.

Two to three percent of individuals receiving variolation ended up dying from smallpox. The only reason this practice continued was because the chance of dying from smallpox caught “naturally” from another infected person was much higher with some epidemics killing 30% or more of victims.

In 1717, Lady Mary Mortley Montagu, was in Constantinople as the wife of the British ambassador. She herself had suffered from smallpox and also lost a brother to the disease. She found that the Turks had another approach to gaining smallpox immunity, inoculation. The word is derived from the Latin inoculare, meaning “to graft.” Inoculation referred to the subcutaneous instillation of smallpox virus into non-immune individuals. The inoculator usually used a lancet wet with fresh matter taken from a ripe pustule of a person who suffered from smallpox. The material was then introduced into the arms or legs of the non-immune person.

Lady Montagu had two of her own children inoculated, one while in the Ottoman Empire and the other upon returning to England. A number of prisoners and later some abandoned children were subjected to the procedure; both Lady Montagu and the Princess of Wales were involved in this "research project," which next had those inoculated deliberately exposed to smallpox. None of them got the disease.

After this success, members of the British royal family were inoculated and the practice spread widely in Europe, reaching America with Reverend Cotton Mather being a strong supporter.

During one of Boston's succession of smallpox epidemics, after hearing from Cotton Mather of a publication in the Transactions of the Royal Society, Dr Zabdiel Boylston, in spite of strenuous protests from the general public and from other physicians, inoculated his own son and two family servants. Eventually he performed the procedure on 247 ranging in age from nine months to sixty-seven years; other physicians inoculated 39, and of the 286 only six died (2%) and three may have already had smallpox, while 14% of the 5,759 who had not been inoculated and caught the disease perished.

Thanks to Edward Jenner

The next step came from Dr. Edward Jenner, who had speculated about the protective effects of cowpox during his "apprenticeship" with George Harwicke. He had heard a woman who was a dairymaid and had a pock-free complexion say, "I shall never have smallpox because I have had cowpox." Over ten years later, in 1796, he used material from a cowpox-infected woman to inoculate an eight-year-old boy. The child recovered from cowpox, but when deliberately inoculated later with smallpox did not develop any signs or symptoms of the much more serious disease.

Since the Latin word for cow is vacca, Jenner dubbed the process vaccination and after being rejected for publication by the Royal Society, sponsored his own booklet to promote the method of smallpox prevention.

The rest, as they say, is history and Jenner became famous; in 1802 he received a large sum of money from Parliament and a still larger one in 1807. He continued his research in several areas of medicine and science and was appointed Physician Extraordinary to the King.

I wanted to write a post about the 1979 and 2001 anthrax attacks, but, as usual, decided that I should read about and write about the the background concepts first. I found a paper titled, "A History of Biological Warfare from 300 B.C.E. to the Present" written by an associate professor of respiratory care at Long Island University and decided I'd start there.

Our earliest reference to biological warfare concerns the Scythians, a tribe of nomads who migrated from Central Asia to Southern Russia in the 8th and 7th century BCE, founding an empire that lasted several centuries. Their prowess in war and their horsemanship were admired, but their archers were also a formidable force, using arrows dipped in the decomposed bodies of venomous snakes as well as in a mixture of decayed human blood and feces. This concoction would have had both snake venom and several deadly forms of bacteria.

A later episode of bio-warfare came in the 14th century when the Mongol army besieged the Crimean city of Caffa. The Tarters hurled cadavers into Caffa, having suffered from an epidemic of plague themselves. In doing so they not only got rid of their dead, but transmitted the disease to the inhabitants of Caffa. A memoir by the Genoese writer Gabriele de' Mussi which covers the war has been reviewed by Mark Wheelis, an emeritus professor of microbiology at UC Davis. He concludes that the Black Plague pandemic of that time period likely spread from the Crimea to Europe. It's still questionable if the Genoese traders in the city were the ones who brought the plague back.

Hannibal is famous for his use of elephants in the war between Carthage and Rome. He also used poisonous snakes, concealed in earthen jars and hurled onto opposing ships during a naval battle in 184 BCE against the leader of Pergomon.

Smallpox was used as a weapon in the French and Indian Wars (1754-1767). The outbreak of the disease at Fort Pitt led to a plan conceived by Colonel Henry Bouquet and General Jeffery Amherst. The British gave their enemies blankets and a handkerchief, all contaminated with pus from the sores of infected British troops, at a peace conference. Many other Indian tribes caught smallpox eventually, but this episode was a deliberate attempt to use the virus to gain advantage in a wartime situation.

And this prison is safer than Unit 731

In World War II, the Japanese Army established the infamous Unit 731. The country had refused to sign the 1925 Geneva Convention ban on biological weapons and in 1932, after Japan invaded Manchuria, an army officer and physician named Shiro Ishii was put in charge of the "Anti-epidemic Water Supply and Purification Bureau." a euphemism for a prison camp for bio-warfare research.

He and his staff spent years experimenting with many the world's most deadly diseases, using Chinese prisoners as guinea pigs for cholera, plague and dysentery. Over 10,000 of the victims died. Field trials included spraying bacterial cultures from airplanes over eleven Chinese cities.

Ishii was eventually replaced as head of the unit by Kitano Misaji, who later became Lieutenant Surgeon General; after the war the United States granted both immunity from war crimes prosecution in exchange for their bio-warfare knowledge. Ishii had faked his own death and gone into hiding, but was captured and interrogated. Neither man's information proved to be of much value in the long run. Ironically Misaji later worked for the Japanese pharmaceutical company Green Cross, becoming the chief director of the company in 1959.

I've skipped many vignettes, but it's time to get to the modern era, returning to anthrax as a major subject to discuss.